mu O-conotoxin MrVIB selectively blocks Na(v)1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits

Ekberg, J., Jayamanne, A., Vaughan, C. W., Aslan, S., Thomas, L., Mould, J., Drinkwater, R., Baker, M. D., Abrahamsen, B., Wood, J. N., Adams, D. J., Christie, M. J. and Lewis, R. J. (2006) mu O-conotoxin MrVIB selectively blocks Na(v)1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits. Proceedings of The National Academy of Sciences of The United States of America, 103 45: 17030-17035. doi:10.1073/pnas.0601819103


Author Ekberg, J.
Jayamanne, A.
Vaughan, C. W.
Aslan, S.
Thomas, L.
Mould, J.
Drinkwater, R.
Baker, M. D.
Abrahamsen, B.
Wood, J. N.
Adams, D. J.
Christie, M. J.
Lewis, R. J.
Title mu O-conotoxin MrVIB selectively blocks Na(v)1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits
Journal name Proceedings of The National Academy of Sciences of The United States of America   Check publisher's open access policy
ISSN 0027-8424
Publication date 2006-11-07
Sub-type Article (original research)
DOI 10.1073/pnas.0601819103
Open Access Status Not Open Access
Volume 103
Issue 45
Start page 17030
End page 17035
Total pages 6
Editor N. R. Cozzarelli
Place of publication Washington
Publisher National Academy of Sciences
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
320704 Cellular Nervous System
730104 Nervous system and disorders
Abstract The tetroclotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that mu O-conotoxin MrVIB from Conus marmoreus displays substantial selectivity for Na(v)1.8 and inhibits pain behavior in models of persistent pain. In rat sensory neurons, submicromolar concentrations of MrVIB blocked tetroclotoxin-resistant current characteristic of Na(v)1.8 but not Na(v)1.9 or tetroclotoxin-sensitive VGSC currents. MrVIB blocked human Nav1.8 expressed in Xenopus oocytes with selectivity at least 10-fold greater than other VGSCs. In neuropathic and chronic inflammatory pain models, allodynia and hyperalgesia were both reduced by intrathecal infusion of MrVIB (0.03-3 nmol), whereas motor side effects occurred only at 30-fold higher doses. In contrast, the nonselective VGSC blocker lignocaine displayed no selectivity for allodynia and hyperalgesia versus motor side effects. The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists.
Keyword Neurosciences
Electrophysiology
Pain Model
Dorsal Root Ganglia
Allodynia
Delta-conotoxin
Neuropathic Pain
Inflammatory Pain
Delta-conotoxins
Expression
Rat
Hyperalgesia
Involvement
Pathways
Sns/pn3
Fibers
Q-Index Code C1

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 106 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 128 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 19:52:49 EST